Almlöf et al. detected by WGS a significant enrichment of ultra-rare (≤0.1%) missense and nonsense mutations in 22 genes known to cause monogenic forms of SLE and seven ultra-rare, coding heterozygous variants in five genes (C1S, DNASE1L3, DNASE1, IFIH1, and RNASEH2A) involved in monogenic SLE. The gene discussed is C1S; the disease is systemic lupus erythematosus.